RGD Reference Report - Association of XPO1 Overexpression with NF-κB and Ki67 in Colorectal Cancer. - Rat Genome Database

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Association of XPO1 Overexpression with NF-κB and Ki67 in Colorectal Cancer.

Authors: Aladhraei, Mohammed  Kassem Al-Thobhani, Abdulla  Poungvarin, Naravat  Suwannalert, Prasit 
Citation: Aladhraei M, etal., Asian Pac J Cancer Prev. 2019 Dec 1;20(12):3747-3754. doi: 10.31557/APJCP.2019.20.12.3747.
RGD ID: 151665794
Pubmed: PMID:31870117   (View Abstract at PubMed)
PMCID: PMC7173379   (View Article at PubMed Central)
DOI: DOI:10.31557/APJCP.2019.20.12.3747   (Journal Full-text)


OBJECTIVES: Exportin 1(XPO1), a nuclear exporter protein, has been gaining recognition in cancer progression and treatment. This study aimed to evaluate the association between the overexpression of XPO1 with NF-κB, Ki67 and clinicopathological characteristics in colorectal cancer (CRC) tissue samples and to explore the anti-proliferative effect of KPT-330, as XPO1 inhibitor, in colorectal cancer cell line.
METHODS: Forty CRC tissue samples were analyzed by immunostaining for the expressions of XPO1, NF-κB and Ki67 and then the anti-proliferative effect of the KPT-330 was also evaluated in HT29 colorectal cancer cell line.
RESULTS: XPO1 overexpression was observed in 52.5% of CRC and significantly apparent with strong intensity in tumor cells compared to the normal adjacent epithelium (P<0.001). Regarding to the histopathological characteristics, the XPO1 overexpression significantly associated with advanced tumor stages (P=0.049) and has great tendency towards moderate/poorly differentiated tumors. Although the XPO1 overexpression was strongly associated with high Ki67 expression (P=0.001), only Ki67 expression showed significant association with tumor size (P=0.012). No significant association was detected between the XPO1 overexpression and NF-κB, while the NF-κB positive expression was significantly associated with lymph node metastasis and Ki67 expression at P=0.027 and P= 0.007, respectively. The in vitro experiments showed a great impact of KPT-330, as XPO1 inhibitor, to inhibit cancer growth in dose and time dependent manner and significantly diminished the colony formation (P<0.001) of HT29 cells- associated with the expression of Ki67 (P<0.001).
CONCLUSION: XPO1 overexpression and NF-κB expression may serve as potential biomarker associated with CRC pathogenesis and proliferation, while the KPT-330 is effectively inhibited-colon cancer growth in vitro. Further studies considering the prognostication role of XPO1 overexpression in CRC are required.
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RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
XPO1Humancolorectal carcinoma disease_progressionIEP protein:increased expression:colorectum (human)RGD 
Xpo1Ratcolorectal carcinoma disease_progressionISOXPO1 (Homo sapiens)protein:increased expression:colorectum (human)RGD 
Xpo1Mousecolorectal carcinoma disease_progressionISOXPO1 (Homo sapiens)protein:increased expression:colorectum (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Xpo1  (exportin 1)

Genes (Mus musculus)
Xpo1  (exportin 1)

Genes (Homo sapiens)
XPO1  (exportin 1)


Additional Information